The characteristics of mass spectrometry have raised it to an outstanding position among the various analysis methods. It has excellent sensitivity and detection limits and may be used in a wide variety of applications, e.g. atomic physics, reaction physics, reaction kinetics, geochronology, biomedicine, ion-molecule reactions, and determination of thermodynamic parameters (ΔG°f, Ka, etc.). Mass spectrometry technology has thus begun to progress very rapidly as its uses have become more widely recognized. This has led to the development of entirely new instruments and applications.
Different types of mass analyzers have been found suitable for different needs, each type having its own unique benefits and deficits. One type of mass analyzer that has been found useful in a wide range of existing and newly developed applications is the time-of-flight mass analyzer. Time-of-flight (TOF) mass spectrometers are routinely used for the analysis of high-molecular weight compounds in a variety of fields of study, including DNA and protein analysis. Although time-of-flight instruments are usually large and expensive due to the nature of the technique, the analysis times are typically short because there is no need to scan through an m/z range to get results. The analytes are typically analyzed concurrently and are distinguished by their velocities, which determine the flight time to a detector.
FIG. 1 illustrates the basic components of a time-of-flight mass spectrometer 20. In operation the time-of-flight mass spectrometer 20 works by measuring the time it takes an ion to travel a distance L along an ion flight path. Typically, this distance corresponds to the length of the flight path traveled by the ion from a position proximate an ion source 25 to an ion detector 30. All ions are accelerated in the same electric field so initial velocities are directly proportional to their mass/charge ratio (m/z). Ions with a low m/z have higher velocities than those with higher m/z and reach the detector 30 sooner. The equation describing this relationship is the simple time-distance equation:tof=L/va=L/[2zQV/m]1/2  (Equation 1)where tof is flight time, L is measured distance through which the ions travel in the ion flight path, va is the velocity of the ions after acceleration, m is mass, z is the number of charges on the molecule, Q is the magnitude of the electric charge and V is the accelerating potential.
Notably, time-of-flight mass spectrometers are quite large since the ions must have a long flight path if the measured time-of-flight values are to be meaningful. Path lengths on the order of one to two meters are necessary to insure that ions of slightly different m/z are resolved. The flight time under typical conditions for ions in the 1000 m/z range is about 70 microseconds and flight time differences at the highest resolution are on the order of nanoseconds.
Some of the factors affecting flight time include the initial ionization and acceleration conditions as well as the m/z of the ion. If large amounts of energy are used or if large accelerations are applied, the flight times will be short and differences in the flight times between ions of similar m/z will be slight. However, despite the negative effect of imparting such high levels of energy to the ions, it is often necessary to give the ions that are to be analyzed high acceleration potentials (up to ˜30 kV) so that the differences in the initial conditions (i.e., kinetic energy spread) of identical ions are minimized. With reference again to FIG. 1, some time-of-flight mass spectrometers may be equipped with a reflectron 35 to compensate for such variations in the initial kinetic energy of ions having the same m/z.
As the uses of time-of-flight mass spectrometry have increased, so too have the requirements for increased mass sensitivity and resolution that are imposed upon these instruments. Because the flight time of the ions along the flight path is short, especially with reasonably sized instruments, compounds of similar m/z are difficult to distinguish and, as such, relatively low resolutions on the order of only several hundreds are typical of these instruments. The resolution may be increased by lengthening the flight path L so that molecules of similar size traveling at slightly different velocities may be separated. Lengthening of the flight path L, however, has traditionally been accomplished by increasing dimension D of the analyzer 20 thereby leading to substantially larger instruments. Thus, development trends with respect to time-of-flight mass spectrometers have gone in the direction of large, increasingly complex designs requiring highly specialized components and tight manufacturing tolerances.